Chemical method of making a suspension, emulsion or dispersion of pyrithione particles

ABSTRACT

A method for producing a suspension, emulsion or dispersion of de-agglomerated particles (advantageously submicron-sized particles) of pyrithione salts comprising contacting agglomerated pyrithione salt particles with a de-agglomerating agent to produce the desired de-agglomerated pyrithione salt particles. Also disclosed is a method for making de-agglomerated submicron-sized particles of pyrithione salts comprision a heating step. Also disclosed are the particles made by the above methods and compositions comprising the particles and a base medium.

This application claims the benefit of U.S. provisional application No.60/123,066, filed Mar. 5, 1999.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to methods for preparingparticles (advantageously submicron-sized particles) of pyrithionesalts, and, more specifically, to methods of preparing such particlesusing de-agglomeration procedures subsequent to production of theparticles. The present invention also relates to products made withthese particles.

2. Description of the Related Art

Polyvalent metal salts of pyrithione (also known as1-hydroxy-2-pyridinethione; 2-pyridinethiol-1-oxide; 2-pyridinethione;2-mercaptopyridine-N-oxide; pyridinethione; and pyridinethione-N-oxide)are known to be effective biocidal agents, and are widely used asfungicides and bactericides in paints and personal care products such asanti-dandruff shampoos. The polyvalent metal salts of pyrithione areonly sparingly soluble in water and include magnesium pyrithione, bariumpyrithione, bismuth pyrithione, strontium pyrithione, copper pyrithione,zinc pyrithione, cadmium pyrithione, and zirconium pyrithione. The mostwidely used divalent pyrithione salts are zinc pyrithione and copperpyrithione.

Zinc and copper pyrithione are useful as antimicrobial agents and areactive against gram-positive and negative bacteria, fungi, and yeasts.Zinc pyrithione is used as an antidandruff component in shampoos, whiletechnical suspensions of zinc pyrithione and/or copper pyrithione areused as preservatives in paints and polymers. Synthesis of polyvalentpyrithione salts are described in U.S. Pat. No. 2,809,971 to Berstein etal. Other patents disclosing similar compounds and processes for makingthem include U.S. Pat. Nos. 2,786,847; 3,589,999; 3,590,035; 3,773,770.

Known methods for producing insoluble polyvalent salts of pyrithioneresult in platelet-shaped (or other irregular shaped) particles havingan average size greater than 1 micrometer (μm), and more frequently inthe range of 3 to 5 μm. These particles are either used directly, or canbe converted into smaller particles. Smaller particles of pyrithionesalts (i.e., less than 1 micrometer or “submicron”) are often desiredbecause they more easily form suspensions, emulsions, or dispersions,and provide a larger surface area for enhanced biocidal activity. Inaddition, smaller particles, particularly in the low submicron range(e.g., below about 0.2 μm are believed to be semi-transparent to light,and below 0.1 μm will be transparent to light). This transparencyprovides the opportunity to manufacture “clear” products, such as clearshampoos and soaps, that are popular in the marketplace today, whileproviding the larger surface area desired for enhanced biocidalefficacy.

Submicron-sized particles of pyrithione salts are usually generated by aseparate mechanical manipulation step (e.g., grinding or crushing) oflarger particles or crystals that are made by conventional processes.For example, European Patent Application No. 70046 describes a processfor the preparation of zinc pyrithione using organic solvents. Thisprocess results in production of large crystals of zinc pyrithione. Aseparate, optional grinding step is used to grind the large crystals andproduce zinc pyrithione particles of smaller size. In another example,U.S. Pat. No. 4,670,430 describes a process of making zinc pyrithioneparticles with a median size of about 0.2 μm or less by mechanicalgrinding of larger particles of zinc pyrithione to the desired submicronsize. Unfortunately, mechanical grinding of large pyrithione particlesinto a submicron sized pyrithione particles tends to not producesubmicron-sized particles having a desired uniform size, shape andnarrow particle size distribution. Such desired parameters are importantsince they are useful in rendering the behavior of the particles inconsumer products, such as shampoos and coatings, predictable. Inaddition, grinding generally results in substantial loss of usefulproduct and is costly in terms of the equipment, time, and energyrequired to provide the ground particles. Moreover, a desired particleshape for pyrithione particles, such as rods, needles, or other shapeswith potentially enhanced biocidal activity, cannot easily be selectedand produced by using grinding methodology.

Submicron-sized particles of pyrithione salts made by the methods of theprior art also suffer from severe agglomeration in which many of thesubmicron-sized particles bond together through noncovalent interactionsto form larger particles of greater than 1 micron in size. Due to highmass, these large agglomerated particles tend to settle out of mostconsumer products over time and result in a hard packed layer ofpyrithione salt that is difficult to re-disperse.

What is needed in the art is a method for producing non-agglomerated orde-agglomerated particles, advantageously having a submicron size orlarger, of pyrithione salts possessing a uniform size, shape and/or sizedistribution. Desirably, the particles, incorporated into a solution,suspension or dispersion, are stable against settling out or agglomerateover time during shipping or storage prior to use. In addition, it isdesired that the particles do not exhibit the damage that is typicallyassociated with mechanical grinding. The present invention is believedto provide answers to these needs.

SUMMARY OF THE INVENTION

In one aspect, the present invention relates to a method for producing asuspension, emulsion, or dispersion of de-agglomerated (advantageouslysubmicron-sized) particles of pyrithione salts, comprising contactingagglomerated pyrithione salt particles with an de-agglomerating agent,optionally in the presence of sonic energy, to produce said suspension,emulsion, or dispersion of de-agglomerated particles of pyrithionesalts.

In another aspect, the present invention provides a method for makingde-agglomerated submicron-sized particles of pyrithione salts comprisingthe steps of:

a) filtering large particles of pyrithione salts is having a particlesize in a range of from 1 to 50 microns to provide filtered particles,

b) contacting the filtered particles with at least one de-agglomeratingagent selected from the group consisting of electrolytes, surfactants,dispersants, and combinations thereof, to provide a suspension ordispersion of de-agglomerated particles, and

c) heating said de-agglomerated particles to an elevated temperature ofat least 60 degrees Centigrade in order to cause a reduction in the sizeof the de-agglomerated particles to a submicron size, thereby producingsaid de-agglomerated submicron-sized particles of pyrithione salts.

In yet another aspect, the present invention relates to a suspension,emulsion, or dispersion of de-agglomerated pyrithione particles made bythe above methods.

In yet another aspect, the present invention relates to a personal carecomposition comprising at least one component selected from the groupconsisting of shampoo, soap, skin care medicament, and combinationsthereof, and additionally comprising an antimicrobially effective amountof de-agglomerated particles made by any of the above methods.

These and other aspects will become apparent upon reading the followingdetailed description of the invention.

DETAILED DESCRIPTION OF THE INVENTION

It now has been surprisingly found, in accordance with the presentinvention, that a solution is provided to the problem of producingdispersions of nonagglomerated (advantageously submicron-sized)particles of pyrithione salts. The present inventors have solved thisproblem by treating particles of pyrithione salts made in a conventionalmanner with a deagglomerating agent that disperses agglomeratedpyrithione salt particles and forms a uniform dispersion ofsubmicron-sized particles of pyrithione salts that do not settle outover time. De-agglomerated particles produced in accordance with themethod of the present invention also display a narrow size distributionthat make them ideal for use in many consumer products, such asshampoos, coatings, and the like.

The present inventors have unexpectedly discovered that agglomeratedparticles of pyrithione salts result in part from non-covalent molecularinteractions, such as ionic attraction between small particles, and thatthese non-covalent interactions can be neutralized by treatingagglomerated particles made by prior art methods with a de-agglomeratingagent. For purposes of the present invention, the de-agglomerating agentmay be a surfactant, an electrolyte, a dispersant, or a combination ofthese. The method of the present invention produces a dispersion,suspension or emulsion comprising particles of pyrithione salts andhaving numerous advantages when incorporated into personal careproducts, such as antidandruff shampoos, soaps, and the like. Forexample, a dispersion of submicron-sized pyrithione salt particlespossesses enhanced biocidal activity, relative to such particles havinga larger size, due to an increased surface area per unit volume. Inaddition, the submicron-sized particles that are suitably generatedaccording to the method of the present invention do not re-agglomerateand remain homogeneously dispersed in solution. Prevention ofre-agglomeration of the particles is particularly important in theproduction of personal care products because agglomerated particles, orthose that are prone to agglomerate, tend to settle out over time andproduce a dense layer of particles on the bottom of containers resultingin an unappealing product having limited utility.

The present inventors have also surprisingly discovered that applicationof heat (at a temperature of at least 60 degrees Centigrade) to needleshaped pyrithione salt particles having particle sizes in the range of1-50 microns causes the particles to decrease in size to the submicronrange. This finding is particularly advantageous since the needles areeasily filtered to remove impurities, whereas submicron-sized pyrithionesalt particles are difficult to filter. Therefore, filtration of theneedles, followed by de-agglomeration of the needles, and heating toproduce the desired purified, submicron-sized particles should provefruitful to the pyrithione salts manufacturing community.

As used herein, the term “submicron-sized particles” refers to particleshaving an average diameter of less than one micron. The term“suspension, emulsion, or dispersion” is refers to a homogeneoussolution of particles that do not settle out or precipitate over time.The term “agglomerated pyrithione salt particles” refers to particles ofpyrithione salts that are bound together by non-covalent forces, such asionic interactions. The term “deagglomerated particles” refers toparticles that are not bonded together by non-covalent forces. The term“de-agglomerating agent” refers to any agent that neutralizes or reducesthe non-covalent forces in agglomerated particles.

The term “sonic energy” is broadly defined to encompass sound waves inthe audio sound spectrum, infrasound spectrum, and ultrasound spectrum,preferably in the frequency range of from 20 Hz to 900,000 Hz (900 kHz)with power levels in the range from about 20 to about 5000 watts, morepreferably 100 to 1000 watts, most preferably 250 to 750 watts, anddecibel (dB) levels from about 10 dB to about 180 dB, preferably 50 to100 dB, most preferably 65 to 85 dB. The term “sonication”, as usedherein, refers to application of sonic energy.

As used herein, the term “water-soluble salts of pyrithione” or“water-soluble pyrithione salts” include those salts of pyrithione inwhich the hydrogen atom of the thiol group is substituted with amonovalent cation. The term “water-soluble polyvalent metal salt” refersto those water-soluble salts in which the cation has a charge of +2 orgreater. The terms “particles of pyrithione salts” or “pyrithione saltparticles” as used herein refer to those salts of pyrithione that formprecipitates and are essentially insoluble or sparingly soluble in thesurrounding medium. The term “dispersant” as used herein refers to acompound that promotes uniform and maximum separation of extremely finesolid particles (i.e., colloidal size), and that does not promotefoaming.

An aspect of the present invention relates to a method for treatingagglomerated pyrithione salt particles made according to known methodswith a de-agglomerating agent to produce a suspension, emulsion, ordispersion of particles (advantageously submicron-sized) particles ofpyrithione salts.

Pyrithione salt particles may be made by any process known in the art.In one embodiment, pyrithione or a water-soluble salt of pyrithione isreacted with a water-soluble salt of a selected polyvalent metal in thepresence of a dispersant to form pyrithione salt particles as aprecipitate. Pyrithione in its acid form, or a water-soluble salt ofpyrithione may be used in the reaction. Useful water soluble salts ofpyrithione preferably include an ammonium ion or an alkali metal ionsuch as sodium. Accordingly, exemplary water soluble salts of pyrithioneinclude sodium pyrithione, potassium pyrithione, lithium pyrithione,ammonium pyrithione, and combinations of these. The most preferredwater-soluble salt of pyrithione useful in the present invention is thesodium salt (i.e., sodium pyrithione). The amount of pyrithione orwater-soluble salt of pyrithione can vary over a wide range andestablishing a useful amount is within the capabilities of the ordinaryskilled practitioner based on the stoichiometry of the reaction and therequired amount of particles that must be generated. A preferred amountof pyrithione or water-soluble pyrithione salt is from about 3% to about52% by weight of the total weight of the reaction mixture.

Exemplary water-soluble polyvalent metal salts useful in accordance withthe method of the invention include example zinc salts, tin salts,cadmium salts, copper salts, silver salts, zirconium salts, magnesiumsalts, aluminum salts, and the like. Combinations of these salts mayalso be employed. Useful counterions for these metals include nitrates,acetates, sulfates, halides or combinations thereof. Preferredwater-soluble polyvalent metal salts include zinc chloride (ZnCl₂),copper chloride (CuCl₂), zinc acetate (Zn(O₂CCH₃)₂) and zinc sulfate(ZnSO₄) . The amount of water-soluble polyvalent metal salt can varydepending on the amount of water-soluble salt of pyrithione. The molarratio of pyrithione or water-soluble salt of pyrithione to thewater-soluble polyvalent metal salt is generally in the range from about1:2 to about 1:8. Preferably, a slight stoichiometric excess (e.g., 5%of water-soluble polyvalent metal salt by weight over pyrithione orwater-soluble salt of pyrithione) is desirable to ensure a completereaction.

Useful media or carriers for the reaction include aqueous media such aswater, or water in combination with one or more organic solvent(s).Useful organic solvents include alcohols, such as methanol, ethanol,amines such as diethanolamine, ether, esters, and the like.

Optional ingredients such as dispersants, surfactants, pearlizing agents(e.g., TiO₂-coated mica), and the like, may also be included in thereaction mixture singly or in any combination. Exemplary dispersantsinclude salts of polymerized alkyl naphthalene sulfonic acids, such as“DARVAN 1” (sodium naphthalene sulfonic acid formaldehyde, a product ofR.T. Vanderbilt Co. Inc.), “DEMOL N” (sodium salt of naphthalenesulfonic acid, a product of Kao Chemicals), “DAXAD 11” (sodium salt ofpolymerized alkyl naphthalene sulfonic acids, a product of W.R. Grace &Co.), “TAMOL N” (sodium salt of condensed naphthalene sulfonic acid, aproduct of Rohm and Haas Co.), “HAROL KG” (potassium salts ofpolymerized alkyl naphthalene sulfonic acids, a product of GradenChemical Co.), “HAROL RG-71” (sodium salts of polymerized alkylnaphthalene sulfonic acids, a product of Graden Chemical Co.), “LOMARLS” (sodium salt of condensed mononaphthalene sulfonic acid, a productof Henkel Corp.) and the like.

Exemplary surfactants include nonionics, anionics, cationics, andamphoterics (the latter being also commonly referred to as“zwitterionics”). Nonionic surfactants include linear alcoholalkoxylates, such as the linear alcohol ethoxylates,ethyoxylated/propoxylated block copolymers, ethyoxylated/propoxylatedfatty alcohols, and polyoxyethylene cetyl ethers, and the like. Usefulanionic surfactants include alkyl diphenylether disulfonates, alkylphenyl ethoxylated phosphate esters, carboxylated linear alcoholalkoxylates, linear alkyl benzene sulfonic acid, diisobutylsulfosuccinate, alkyl sulfonates, and the like. illustrative cationicsurfactants include alkyl triammonium halide, non-linear alkyl dimethylhalide, alkyl dimethyl benzyl ammonium halide-containing surfactants,and the like. Illustrative amphoteric surfactants include polyglycolether derivatives, ethoxylate oxazoline derivatives, lauramidopropylbetaine, lecithin, and the like.

Generally, these ingredients are utilized in the methods of the presentinvention in a pyrithione salt-dispersing effective amount, preferablyan amount of from about 0.1 to about 20% by weight, more preferably fromabout 0.1 to about 5% by weight, and most preferably from about 0.1 toabout 6% by weight, all based on the total weight of the reactionmixture.

The temperature of the reaction may be any temperature which permitsprecipitation of particles of pyrithione salt. Preferable temperaturesfor the reaction are in the range of from between about 4 and about 100°C., more preferably between about 25 and about 68° C., and mostpreferably between about 30° C. and about 35° C.

In addition, the reaction may be gently agitated to promote formation ofthe particles. Generally, gently stirring the reaction at 150 rpm orless, and preferably about 100 rpm, after all the ingredients have beencombined is sufficient to promote formation of the particles.

Additional inorganic salts, such as potassium chloride, sodium chloride,magnesium chloride, the corresponding sulfates, citrates, nitrates, andthe like, may be added to the reaction medium to control particle lengthand shape. For example, suitable addition of salts can result inparticles of pyrithione salts having a variety of advantageous shapes,including nonspherical or non-platelet form, such as rods, needles,cylinders, cones, ellipsoids, prisms, parallelepipeds, pyramids, and thelike. The particles formed by the present invention may also take theform of tetrahedrons, hexahedrons (cube), octahedrons, dodecahedrons,icosahedrons, and the like. The present inventors have observed thatcertain shapes of pyrithione salt particles offer advantages of increasebiocidal activity due to increased surface area.

Preferably, the additional salts are included in the reaction mixturefrom 0.1% by weight to about 10% by weight, more preferably from about1% by weight to about 8% by weight, and most preferably from about 3% byweight to about 6% by weight, all based on the total weight of thereaction mixture.

A particularly useful amount of additional sodium chloride added to thereaction mixture to control particle size and shape is 5% by weightbased on the total weight of the reaction mixture.

In one order to produce the elongated particles of the invention,pyrithione or a selected water-soluble salt of pyrithione and a selectedwater-soluble polyvalent metal salt are reacted in the presence of asurfactant or combination of surfactants in any suitable reaction vesselat a temperature below 70° C., and preferably between about 10° C. and68° C. In a preferred embodiment, sodium pyrithione is reacted with zincchloride or zinc sulfate in the presence of salt (e.g., sodium chloride)and a selected surfactant or combination of selected surfactants atabout 35° C. to form zinc pyrithione having rod or needles shapes, alongwith aqueous sodium chloride or aqueous sodium sulfate as by-products.The particles may also be utilized in a “continuous” process in whichthe zinc pyrithione particles are collected, and the mother liquorcontaining aqueous sodium chloride or sodium sulfate is recycled back tothe reaction vessel to provide a source of additional salt. An optionalfilter (e.g., carbon or charcoal filter) may be employed to removeimpurities such as colored organic compounds from the mother liquor.Particles of zinc pyrithione so formed have a “needle” or “rod”appearance. Generally, the rods or needles of zinc pyrithione saltproduced in accordance with the present invention are between about 0.1and about 1 μm in width and between about 2 and about 50 μm in length.Accordingly, the aspect ratio of the elongated particles is greater thanabout 1, and more preferably from about 2 to about 500.

The pyrithione salt particles may be isolated from the mother liquor byfiltration, centrifugation, sedimentation, or other isolation methodsknown in the art. Subsequent procedures, such as grinding, may also beperformed. Alternatively, the agglomerated particles in the reactionmedium may be treated with a deagglomerating agent directly.

During particle formation, either by the above exemplary method or byother methods known in the art, the individual pyrithione salt particlesaggregate into larger agglomerates having sizes greater than about 1micron. To reduce or eliminate this aggregation and to obtain apopulation of individual particles having sizes of less than 1 micron,the aggregated particles are treated with a deaglommerating agent toproduce a dispersion of submicron-sized particles of pyrithione salts.

The deagglomerating agent used in the method of the present inventionmay be any agent that separates agglomerated particles of pyrithionesalt. Examples of such deagglomerating agents include electrolytes,surfactants, sonic energy, and combinations of these. The inventors haveunexpectedly found that treatment of agglomerated particles with adeagglomerating agent neutralizes the noncovalent forces that result inagglomeration of the particles, and results in production of apopulation of pyrithione salt particles having sizes of less than 1micron.

Electrolytes used as a deagglomerating agent in the method of thepresent invention include alkali metal or alkaline earth metal salts(e.g., alkali metal or alkaline earth metal salts of chloride, sulfate,carbonate, citrate, benzoate), alkali metal or alkaline earth metaloxides, alkali metal or alkaline earth metal hydroxides, andcombinations thereof. Particularly useful electrolytes include sodiumchloride, calcium chloride, zince chloride, sodium oxide, calcium oxide,zinc oxide, sodium hydroxide, calcium hydroxide, and zinc hydroxide.Combinations of two, three, four, or more, of these electrolytes mayalso be used in accordance with the method of the present invention.

Preferably, electrolytes used according to the method of the presentinvention range from about 0.01 to 10% by weight, more preferably, fromabout 0.1 to 5% by weight, and most preferably from about 0.5 to 3% byweight, based on the total weight containing the admixture of aggregatedparticles (on a dry weight basis).

Dispersants useful in the present invention include salts of polymerizedor unpolymerized alkyl naphthalene sulfonic acids. Useful salts ofpolymerized alkyl naphthalene sulfonic acids include “DARVAN 1” (sodiumnaphthalene sulfonic acid formaldehyde, a product of R.T. Vanderbilt Co.Inc.), “DEMOL N” (sodium salt of naphthalene sulfonic acid, a product ofKao Chemicals), “DAXAD 11” (sodium salt of polymerized alkyl naphthalenesulfonic acids, a product of W.R. Grace & Co.), “TAMOL N” (sodium saltof condensed naphthalene sulfonic acid, a product of Rohm and Haas Co.),“HAROL KG” (potassium salts of polymerized alkyl naphthalene sulfonicacids, a product of Graden Chemical Co.), “HAROL RG-71” (sodium salts ofpolymerized alkyl naphthalene sulfonic acids, a product of GradenChemical Co.), “LOMAR LS” (sodium salt of condensed mononaphthalenesulfonic acid, a product of Henkel Corp.) and the like. Surfactants usedas a deagglomerating agent in the method of the present inventionanionic surfactants, cationic surfactants, nonionic surfactants,amphoteric surfactants (also known as “zwitterionics”), and the like.

Useful nonionic surfactants include linear alcohol alkoxylates, such asthe linear alcohol ethoxylates, ethyoxylated/propoxylated blockcopolymers, ethyoxylated/propoxylated fatty alcohols, andpolyoxyethylene cetyl ethers, and the like. Useful linear alcoholalkoxylates are commercially available, for example, under theregistered trademark POLY-TERGENT SL-42, a product of Olin Corporation.If desired, the alcohol alkoxylate is suitably end-capped with a loweralkyl group, and such a product is commercially available asPOLY-TERGENT SLF-18, a propylene oxide-capped linear alcohol alkoxylatethat is also a product of Olin Corporation, and these end-capped linearalcohol alkoxylates are notably low foaming during use. Alsoadvantageous for use in accordance with the present invention aresurfactants within the group commercially available as POLY-TERGENTSLF-18B series surfactants, which are surfactants characterized byenhanced biodegradability (also products of Olin Corporation), beingalkene oxide-capped linear alcohol alkoxylates, containing ethyleneoxide moieties in the backbone, and suitably also containing at leastone propylene oxide moiety in the backbone, as disclosed, for example,in U.S. Pat. Nos. 4,925,587 and 4,898,621.

Other useful nonionic surfactants include one commercially available asNEODOL 91-6, a registered trademark surfactant product of ShellChemical. This surfactant is a detergent range mixture of C₉-C₁₁ linearprimary alcohol ethoxylates having an average of six moles of ethyleneoxide per mole of alcohol. Other useful nonionic surfactants includethose containing a linear C₉-C₁₁, carbon chain and five or six ethyleneoxide or propylene oxide groups per molecule.

Useful anionic surfactants include alkyl diphenylether disulfonates,alkyl phenyl ethoxylated phosphate esters, carboxylated linear alcoholalkoxylates, linear alkyl benzene sulfonic acid, diisobutylsulfosuccinate, and alkyl sulfonates. Useful anionics also include thealkylated diphenyl oxide sulfonates, and their methods of preparationare well-known, as illustrated by the disclosures of U.S. Pat. Nos.3,264,242; 3,634,272; and 3,945,437, the disclosures of which are allincorporated herein by reference. Commercial methods of preparation ofthe alkylated diphenyl oxide sulfonates generally do not produce specieswhich are monoalkylated, monosulfonated, dialkylated or disulfonated.The commercially available species typically are predominately (greaterthan 90 percent) disulfonated and are a mixture of mono- anddi-alkylated with the percentage of dialkylation being about 15 to about25 percent, and the percentage of monoalkylation being about 75 to 85percent. Most typically, the commercially available species are about 80percent monoalkylated and 20 percent dialkylated.

Two illustrative commercially available solutions containing alkylateddiphenyl oxide sulfonate surfactants are DOWFAX 8390 and DOWFAX 8390Asurfactants, trademarked products of The Dow Chemical Company. In each,the alkyl group is predominantly a hexadecyl C₁₆ group. These productsare suitably employed in a solution fully or partially neutralized withammonium hydroxide if desired.

An advantageous anionic surfactant is also provided by reacting theabove-described alkylated diphenyl oxide sulfonates with a piperazinecompound to produce a molar ratio of sulfonate compound to piperazinecompound of between about 10:1 and about 1:10, preferably between about2:1 and about 1:2. Although any piperazine compound can be used for suchreaction, preferred compounds include those selected from the groupconsisting of 1,2-aminoethyl piperazine, 1,4-piperazinediethane sulfonicacid, anhydrous piperazine, hydrated piperazine, and combinationsthereof.

Other useful anionics are polycarboxylated alcohol alkoxylates,preferably those selected from acids or organic or inorganic salts ofthe following: polycarboxylated linear alcohol alkoxylates,polycarboxylated branched alcohol alkoxylates, polycarboxylated cyclicalcohol alkoxylates, and combinations thereof. These polycarboxylatedalcohol alkoxylates typically contain at least two succinic acidradicals per molecule. Preferred polycarboxylated alcohol alkoxylatesare those having a backbone containing both poly(propylene oxide) andpoly(ethylene oxide) blocks, and such preferred polycarboxylated alcoholalkoxylates are readily commercially available, for example, asPOLY-TERGENT CS-1, a trademarked surfactant of Olin Corporation. Ifdesired, at least a portion of the acid groups on the polycarboxylatedalcohol alkoxylate are neutralized with a base to provide thecorresponding salt. Suitable bases include alkali metal hydroxides,alkaline earth metal hydroxides, and metal-free hydroxides, includingpotassium hydroxide, ammonium hydroxide, calcium hydroxide, magnesiumhydroxide, ammonia, mono-, di- and tri-ethanol amines, and combinationsthereof. Sodium hydroxide is preferred, and although potassium hydroxidecan be employed, it is not preferred. The organic or inorganic base ispreferably employed in at least an equimolar amount relative to thenumber of moles of polycarboxylated alcohol alkoxylated used. Thepolycarboxylated alcohol may also contain a polycarboxylic acid, forexample, polyacrylic acid, along with the starting alcohol alkoxylateand esters of the alkoxylate of the polycarboxylic acid.

Although individually the cationic and the amphoteric surfactants areacceptable for use in the process of the present invention, they mayalso be used in combination with at least one surfactant from one of theother classes. Illustrative cationics include alkyl triammonium halide,non-linear alkyl dimethyl halide and alkyl dimethyl benzyl ammoniumhalide-containing surfactants. Illustrative amphoteric surfactantsinclude polyglycol ether derivatives, ethoxylate oxazoline derivatives,lauramidopropyl betaine, and lecithin.

Suitable blends can be employed in the process of the present inventionbased on various combinations of the above-described surfactants. Such ablend can be any combination of two or more surfactants, between orwithin the above-described four broad classes of surfactants.Combinations can include blends of: anionic with anionic, anionic withnonionic, anionic with cationic, anionic with amphoteric, cationic withcationic, cationic with amphoteric, nonionic with nonionic, nonionicwith amphoteric, and amphoteric with amphoteric. Likewise, ternary andquaternary blends of surfactants by selecting three or four surfactants,respectively, from within or among the above-described classes.

Suitably, any single or combination of two, three or four surfactantsfrom the following illustrative list are suitably employed: (a)nonionics, including alkoxylated linear alcohols (such as POLY-TERGENTSLF-18 surfactant, a product of Olin Corporation), linear alcoholethoxylates (such as NEODOL 91-8 surfactant, a product of the ShellCorporation), ethoxylated linear alkyl benzene (such as TRITON X-100surfactant, a product of Union Carbide Corporation), and EO/PO blockcopolymers (such. as POLY-TERGENT E-17A surfactant, a product of OlinCorporation); (b) anionics, including alkyl diphenyl ether disulfonates(such as POLY-TERGENT 2A1 surfactant, a product of Olin Corporation),alkyl phenyl ethoxylated phosphate esters (such as Wayfos M-60surfactant, a product of Olin Corporation), carboxylated linear alcoholalkoxylates (such as POLY-TERGENT CS-1 surfactant, a product of OlinCorporation), linear alkyl benzene sulfonic acid (such as BIOSOFT S-130surfactant, a product of Stepan Company), alpha-olefin sulfonates (suchas BIO TERG AS-40 surfactant, a product of Stepan Company),dialkylsulfosuccinates (such as AROWET SC-75 surfactant, a product ofArol Chemical Products), and alkyl sulfates (such as STEPANOL SLSsurfactant, a product of Stepan Company); (c) cationics including alkyltriammonium halides (such as CTAB surfactant, a product of VWRScientific Inc.), polyoxyethylene cocoamine (such as MAZEEN surfactant,a product of PPG Industries), primary alkyl amines (such as ARMEENsurfactant, a product of Akzo Chemical Co.), dicoco dimethyl ammoniumhalide (such as JET QUAT surfactant, a product of Jetco Chemical Inc.),di-isodecyl dimethyl ammonium halides (such as AMMONYX K9 surfactant, aproduct of Stepan Company), and diethyl aminoethyl stearate (such asCERASYNT 303 surfactant, a product of ISP Van Dyke); and, (d)amphoterics, including polyglycol ether derivatives (such as ALBEGAL Asurfactant, a product of Ciba-Geigy), ethoxylated oxazolin derivatives(such as ALKATERG T-IV surfactant, a product of Angus Chemicals),lauramide propyl betain (such as LEXAINE C surfactant, a product ofInolex Chemicals), lecithin (such as CANASPERSE surfactant, a product ofCan Amoral), disocium cocoamphodiacetate (such as MONATERICS surfactant,a product of Mona Industries), complex fatty amine salt (such as MAFO 13surfactant, a product of PPG Industries), and cocoamine oxide (such asMACKAMINE CO surfactant, a product of the McIntyre Group Ltd.).Combinations of two, three, four, or more, of these surfactants may alsobe used in accordance with the method of the present invention.

Preferably, surfactants used according to the method of the presentinvention range from about 0.01 to 10% by weight, more preferably, fromabout 0.025 to 5% by weight, and most preferably from about 0.05 to 1%by weight, based on the total weight of the admixture containingaggregated particles (on a dry weight basis).

Sonic energy is optionally employed in the methods of the presentinvention in order to facilitate or expedite the desiredde-agglomeration being effected by the de-agglomerating agent(s), and toenhance the uniformity of the resulting suspension, dispersion oremulsion. If used, the sonic energy is preferably applied to theagglomerated pyrithione salt particles in the presence of thede-agglomerating agent(s) to form a highly uniform suspension ofnon-agglomerated particles. The sonic energy preferably has a frequencyof from about 20 Hz to about 900,000 Hz (900 kHz), more preferably fromabout 5 kHz to about 105 kHz, and most preferably from about 16 kHz toabout 20 kHz. Combinations of frequencies may also be used, depending onthe configuration of the particular sonication apparatus. The energylevel output that results from the sonic energy applied to the reactionmixture is preferably in the range from about 20 to about 5000 Watts,more preferably from about 100 to about 1000 Watts, and most preferablyfrom about 400 to about 600 Watts. An example of a suitable sonicationdevice that is useful according to is the method of the invention is aNearfield NAP Model 3606 acoustical processor (available commerciallyfrom Advanced Sonic Processing Systems, Woodbury, Conn.), although anysonication device may be employed in the method of the invention.

It will be noted that the sound levels that could be produced using thelevels of sonic energy discussed above can exceed 100 decibels (dB) andpotentially reach levels as high as 140 dB. In order to avoid hearingimpairment, proper safety and sound abatement procedures should beundertaken when decibel levels are greater than about 80 dB.

Preferably, in the batch process, sonic energy is applied to thereaction mixture through a climate probe that is placed in directcontact with the particles after their formation. Other methods ofapplying sonic energy are also feasible, such as a pipe which carriesthe sonic energy to the reaction vessel, or a chamber lined with sonicenergy transducers. The latter method is particularly useful in thecontinuous manufacture of particles as described in copending U.S.patent application Ser. No. (Attorney Docket No. 101715-100, filed onFeb. 23, 1999), incorporated herein by reference in its entirety.

The uniform, well-dispersed suspension of non-agglomerated particlesmade according to the method of the invention is useful in theproduction of personal care products (e.g., shampoos, soaps, etc.),cleaning products, paints, coatings, foodstuffs, fertilizers, poolchemicals, foodstuffs, and the like. For example, deagglomerated zincpyrithione particles made according to the method of the invention are auseful component of antimicrobial-containing shampoos, e.g., as anantidandruff additive in providing an antidandruff efficacycharacteristic to shampoos. Generally, the antimicrobial-containingpersonal care composition of the present invention may contain any “basemedium” component found in shampoos, soaps, or skin care medicaments,such as, for example, glycerine, aloe, surfactants such asdodecyl-benzene sulfonate (“DDBS”), mineral oil, water, and combinationsthereof. Other such components are described in the examples providedhereinbelow.

The following examples are intended to illustrate, but in no way limitthe scope of the present invention. All parts and percentages are byweight and all temperatures are in degrees Celsius unless explicitlystated otherwise. In the following Examples “q.s.” means quantitysufficient, generally 0.1 to 2% by weight.

EXAMPLES Example I Production of Needles of Zinc Pyrithione

To a 1200 g of 6% sodium pyrithione solution was added 6.0 g ofdispersant (sodium salt of polymerized alkyl naphthalene sulfonic acidsold under the tradename DARVAN 1 available from J.T. Vanderbilt) in a3000 ml jacketed cylindrical pyrex reactor. The temperature was raisedto 35° C. and maintained throughout the reaction sequence. 437 g of a10% aqueous zinc sulfate monohydrate solution was pumped into thereactor over 50 to 60 minutes using a peristaltic pump. The productslurry was isolated by filtration with a Buchner funnel and washed withwater.

Upon analysis, the isolated reaction product was about 19.6% zincpyrithione by weight. Under microscopic examination, the isolatedproduct was found to consist of particles of zinc pyrithione having rodor needle shape.

Example 2 Production of Needles of Zinc Pyrithione

A solution of 355 g of 16.9% by weight sodium pyrithione, 845 ml water,and 2.4 g of DARVAN 1 (sodium naphthalene sulfonic acid formaldehyde)was placed in a 2000 ml jacketed reaction vessel and warmed to 39° C. Asolution of 198.5 g of 20% by weight zinc sulfate monohydrate and 595.4ml water was added over about 68 minutes. Following addition of the zincsulfate solution, the mixture was stirred for 20 minutes and the productwas isolated by filtration and washed. The isolated precipitate wasassayed and found to contain about 33.6% by weight zinc pyrithione.

The zinc pyrithione particles were resuspended in an aqueous solution ofwater and DARVAN 1 (sodium naphthalene sulfonic acid formaldehyde) toform solution containing 25% by weight zinc pyrithione and 0.1% byweight DARVAN 1 dispersant. The particles were analyzed on a Horiba 910Particle Size Analyzer. Photomicrographs showed that the particles hadan elongated form and appeared as rods or needles. The width of the rodsand needles varied from about 0.1 to about 1 μm, and the length of therods and needles varied from about 2 to about 10 μm. Repeated particlesize analysis of this product using the Horiba 910 Analyzer over time(i.e, during several days of measurement) indicated that the particlesize distribution did not change. Hence, the agglomerates had beenremoved, and re-agglomeration did not reoccur.

Example 3 De-agglomeration of Agglomerated Zinc Pyrithione Particles

1000 g of 25% aqueous solution of zinc pyrithione particles made inaccordance with the protocol of Examples 1 and 2 above were poured intoa 2 L beaker. 1 gram of DARVAN 1 dispersant and 1 gram of calciumchloride were added respectively to the beaker and mixed with a handmixer for 1-2 minutes at high speed. The contents are then transferredto a 2 liter glass jacketed reactor and gently mixed at about 150 rpmusing Lithinin A320 blades. The reactor was heated to about 65° C. andheld for approximately 15 minutes. Chloroisothiazolone was added as apreservative to a final concentration of approximately 3 ppm duringheating. Approximately 3 minutes after addition of the preservative, theheat is turned off and the mixture is allowed to cool to roomtemperature. The particles are then transferred to a storage containerand analyzed over several days for size, dispersion, color, settlementand agglomeration. The particle size distribution did not change over aperiod of several days (as shown by repeated measurements of the productusing a Horiba 910 Particle Size Analyzer), thus demonstrating that theparticles did not re-agglomerate over time.

Example 4 Deagglomeration of Agglomerated Zinc Pyrithione Particles

1000 g of 25% aqueous solution of zinc pyrithione particles made inExample 1 or 2 above were poured into a 2 L beaker. 0.5 gram ofWITCAMIDE 5130 series surfactant, an alkanolamide nonionic surfactant ofWitco Chemicals, and 10 grams of sodium chloride were added respectivelyto the beaker and mixed with a hand mixer for 1-2 minutes at high speed.The contents are then transferred to a 2 liter glass jacketed reactorand gently mixed at about 150 rpm using Lithinin A320 blades. Thereactor was heated to about 65° C. and held for approximately 15minutes. Methylisothiazolone was added as a preservative to a finalconcentration as needed (approximately 3 ppm) during heating.Approximately 3 minutes after addition of the preservative, the heat isturned off and the mixture is allowed to cool to room temperature. Theparticles are then transferred to a storage container and analyzed overseveral days for size, dispersion, color, settlement, and agglomeration.Again, for this product the particle size distribution did not changeover a period of several days (as shown by repeated measurements of theproduct using a Horiba 910 Particle Size Analyzer), thus demonstratingthat the particles did not re-agglomerate over time.

Example 5 (Proposed Example) Antidandruff Shampoo

Formulation I

An antidandruff shampoo composition is made using de-agglomeratedparticles of zinc pyrithione, prepared as described in Examples 1-4, incombination with the following ingredients:

Component A: Water 41.0%  Magnesium aluminum silicate 1.0% Hydroxypropylmethylcellulose 0.8% Component B: Zinc Pyrithione (25% aqueousdispersion) 4.0% Component C: Cocamide DEA 1.0% Component D:Triethanolamine lauryl sulfate, 40% 40.0%  Triethanolamine, 99% 3.2%FD&C Blue No. 1 (0.2%) 1.5% FD&C Yellow No. 5 (0.1%) 0.5% Fragrance q.s.

The antidandruff shampoo composition is made as follows: Component A isprepared by heating water to 70° C. and dissolving the other twocomponents with stirring (about 1500 rpm). Component B is added, andstirring continued for 5 minutes. Stirring speed was reduce stirring to˜300 RPM. Component C is melted in a separate container, and added tothe A/B mixture. The heat is removed and component D is added while themixture cooled.

Example 6 (Proposed Example) Antidandruff Shampoo

Formulation II

Another antidandruff shampoo composition is made using zinc pyrithionemade as described in Examples 1-4, in combination with the followingingredients:

Component A: Deionized water q.s. Ammonium lauryl sulfate 15.0% Cocamide DEA 2.0% Component B: Di(hydrogenated) tallow phthalic 5.0%acid amide Zinc Pyrithione (25% aqueous dispersion) 4.0% Component C:Preservative q.s. Component D: Citric Acid, 50% aq. Solution, OR q.s.Sodium hydroxide, 50% aqueous solution Component E: Ammonium chlorideq.s.

The antidandruff shampoo composition is made as follows:

In separate containers, components A and B are each mixed well.Component A is heated to 165-170° F. and component B is added. Themixture is stirred for 30 minutes. The mixture is then cooled to 120°F., and component C was added. The pH of the resulting mixture isadjusted to 5.0-6.2 with component D, and the viscosity is adjusted withcomponent E.

Example 7 (Proposed Example) Antidandruff Shampoo with Conditioner I

An antidandruff shampoo and conditioner composition is made using needleand rod forms of zinc pyrithione made as described in Examples 1-4 incombination with the following ingredients:

Component A: Deionized Water q.s. Ammonium. lauryl sulfate 20.0% Cocamide DEA 2.0% Component B: Di(hydrogenated) tallow phthalic 4.0%acid amide Zinc Pyrithione (25% aqueous dispersion) 4.0% Dimethicone,12,000 cps 0.5% Component C: Preservative q.s. Component D: Citric acid,50% aqueous solution, OR Sodium hydroxide, 50% aqueous solution q.s.Component E: Ammonium chloride q.s.

The antidandruff shampoo and conditioner composition is made as follows:

In separate containers, components A and B is each mixed well. ComponentA is heated to 165-170° F. and component B is added. The mixture isstirred for 30 minutes. The mixture is then cooled to 120° F., andcomponent C was added. The pH of the resulting mixture is adjusted to5.0-6.2 with component D, and the viscosity is adjusted with componentE.

Example 8 (Proposed Example) Antidandruff Shampoo with Conditioner II

Another antidandruff shampoo and conditioner composition is made usingneedle and rod forms of zinc pyrithione made as described in Examples1-4 in combination with the following ingredients:

Component A: Deionized water q.s. Guar hydroxypropyl trimonium chloride0.30% Magnesium Aluminum Silicate 0.70% Zinc Pyrithione (25% aqueousdispersion)  4.0% Component B: Sodium laureth sulfate 30.0% Ammoniumxylene sulfonate, 40% aq. 02.0% Component C: Tricetylammonium chloride0.50% Cetyl alcohol NF 0.40% Stearyl alcohol 0.40% Glycol distearate2.00% Component D: Cocamide MEA 1.70% Ammonium lauryl sulfate 36.00% Component E: Preservative 0.05% Fragrance and dye q.s. Component FCitric acid, 25% aqueous solution q.s.

The antidandruff shampoo and conditioner composition is made as follows:

Component A is prepared by heating water to 50° C. and dispersing theguar hydroxypropyl trimonium chloride and the magnesium aluminumsilicate with rapid agitation. The zinc pyrithione dispersion is addedto this combination with stirring. The pH of component A is adjusted to4.5-5.0 with component F. Both components of B are slowly added tocomponent A, mixing well. The pH of the mixture is adjusted to 5.7-6.3with component F. In a separate container, component C is heated to70-75° C. The A/B mixture is heated to 70-75° C. and blend withcomponent C, mixing well. Both components of D are added to the hotmixture, and stirred well. The pH of the mixture are adjusted to 5.7-6.3with component F. The mixture is cooled to 40-45° C., and component Ewas added with stirring. If a higher viscosity is desired, adding0.05-1% sodium chloride can increase the viscosity of the product.

Example 9 (Proposed Example): “Extra Body” Antidandruff Shampoo

An “extra body” antidandruff shampoo and conditioner composition is madeusing needle and rod forms of zinc pyrithione made as described inExamples 1-4 in combination with the following ingredients:

Component A: Deionized Water q.s. Zinc Pyrithione (25% aqueousdispersion)  4.0% Component B: Methyl Paraben 0.30% Propyl Paraben 0.10%Propylene Glycol 0.50% Sodium Chloride 0.50% Component C:Triethanolamine lauryl sulfate 20.0% Cocamide MEA  4.0% Ethylene glycoldistearate  7.0% Component D: Cocodimonium hydroiyzed animal protein1.00% Component E: FD&C Blue No. 1 q.s. Component F: Citric Acid, 50%aqueous solution q.s.

The antidandruff shampoo and conditioner composition are made asfollows:

Component A is heated to 70° C. The ingredients of component B are addedwith good stirring until dissolved. The ingredients of component C areadded to the mixture sequentially, and heated with mixing to 75° C. Themixture is cooled with stirring to 40° C., and components D and E areadded with stirring. The pH of the final composition is adjusted to 4.7with component F.

Although the invention has been shown and described with respect toillustrative embodiments thereof, it should be appreciated that theforegoing and various other changes, omissions and additions in the formand detail thereof may be made without departing from the spirit andscope of the invention as delineated in the claims. All patents andpatent applications mentioned are herein incorporated by reference intheir entireties.

What is claimed is:
 1. A method for producing a suspension, emulsion, ordispersion of de-agglomerated particles of pyrithione salts, comprisingcontacting agglomerated pyrithione salt particles with ande-agglomerating agent, in the presence of sonic energy, to produce saidsuspension, emulsion, or dispersion of de-agglomerated particles ofpyrithione salts.
 2. The method of claim 1, wherein said deagglomeratingagent is selected from the group consisting of electrolytes,surfactants, dispersants, and combinations thereof.
 3. The method ofclaim 2, wherein said dispersant is a salt of polymerized orunpolymerized alkyl naphthalene sulfonic acids.
 4. The method of claim1, wherein each of said particles of pyrithione salts has a size withina range of from 0.01 to 50 microns.
 5. The method of claim 1, whereinsaid admixture of agglomerated pyrithione salt particles is made byreacting pyrithione or a water-soluble salt of pyrithione and awater-soluble polyvalent metal salt in a carrier and in the presence ofa dispersant at a temperature from about 4° C. to about 100° C. toproduce an admixture of agglomerated pyrithione salt particles.
 6. Themethod of claim 5, wherein said water-soluble salt of pyrithione isselected from the group consisting of sodium pyrithione, potassiumpyrithione, lithium pyrithione, ammonium pyrithione, and combinationsthereof.
 7. The method of claim 5, wherein said water-soluble polyvalentmetal salt is a divalent salt selected from the group consisting of zincsalts, tin salts, cadmium salts, copper salts, zirconium salts,magnesium salts, aluminum salts, nitrate salts, acetate salts, sulfatesalts, halide salts, and combinations thereof.
 8. The method of claim 7,wherein said divalent salt is selected from the group consisting of zincsulfate, zinc chloride, zinc acetate, copper chloride, and combinationsthereof.
 9. The method of claim 5, wherein said dispersant is selectedfrom the group consisting of sodium salts of polymerized alkylnaphthalene sulfonic acids and combinations thereof.
 10. The method ofclaim 1, wherein said particles of pyrithione salt have a form selectedfrom the group consisting of rods, needles, cylinders, cones,ellipsoids, prisms, parallelepipeds, pyramids, tetrahedrons, hexahedrons(cube), octahedrons, dodecahedrons,icosahedrons, and combinationsthereof.
 11. The method of claim 1, further comprising the step ofisolating said agglomerated particles of pyrithione salt.
 12. Asuspension, emulsion or dispersion of deagglomerated submicron-sizedpyrithione particles made by the method of claim
 1. 13. A method formaking de-agglomerated submicron-sized particles of pyrithione saltswhich comprises the steps of: a) filtering large particles of pyrithionesalts having a particle size in a range of from 1 to 50 microns toprovide filtered particles, b) contacting the filtered particles with atleast one de-agglomerating agent selected from the group consisting ofelectrolytes, surfactants, dispersants, and combinations thereof, toprovide a suspension or dispersion of de-agglomerated particles, and c)heating said de-agglomerated particles to an elevated temperature of atleast 60 degrees Centigrade in order to cause a reduction in the size ofthe de-agglomerated particles to a submicron size, thereby producingsaid de-agglomerated submicron-sized particles of pyrithione salts. 14.The method of claim 13 wherein the large particles of step a) are in theform of needles.